tetano
Editor, Senior Moderator
ACS Infect Dis
. 2021 May 26.
doi: 10.1021/acsinfecdis.1c00083. Online ahead of print.
Quinoline and Quinazoline Derivatives Inhibit Viral RNA Synthesis by SARS-CoV-2 RdRp
Jianyuan Zhao[SUP] 1 [/SUP], Yongxin Zhang[SUP] 1 [/SUP], Minghua Wang[SUP] 1 [/SUP], Qian Liu[SUP] 1 [/SUP], Xiaobo Lei[SUP] 2 [/SUP], Meng Wu[SUP] 3 [/SUP], SaiSai Guo[SUP] 1 [/SUP], Dongrong Yi[SUP] 1 [/SUP], Quanjie Li[SUP] 1 [/SUP], Ling Ma[SUP] 1 [/SUP], Zhenlong Liu[SUP] 4 [/SUP], Fei Guo[SUP] 2 [/SUP], Jianwei Wang[SUP] 2 [/SUP], Xiaoyu Li[SUP] 1 [/SUP], Yucheng Wang[SUP] 1 [/SUP], Shan Cen[SUP] 1 [/SUP]
Affiliations
Abstract
Coronavirus disease 2019 (COVID-19) is a fatal respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The identification of potential drugs is urgently needed to control the pandemic. RNA dependent RNA polymerase (RdRp) is a conserved protein within RNA viruses and plays a crucial role in the viral life cycle, thus making it an attractive target for development of antiviral drugs. In this study, 101 quinoline and quinazoline derivatives were screened against SARS-CoV-2 RdRp using a cell-based assay. Three compounds I-13e, I-13h, and I-13i exhibit remarkable potency in inhibiting RNA synthesis driven by SARS-CoV-2 RdRp and relatively low cytotoxicity. Among these three compounds, I-13e showed the strongest inhibition upon RNA synthesis driven by SARS-CoV-2 RdRp, the resistance to viral exoribonuclease activity and the inhibitory effect on the replication of CoV, thus holding potential of being drug candidate for treatment of SARS-CoV-2.
Keywords: COVID-19; Quinoline and quinazoline derivatives; RdRp inhibitors; SARS-CoV-2
. 2021 May 26.
doi: 10.1021/acsinfecdis.1c00083. Online ahead of print.
Quinoline and Quinazoline Derivatives Inhibit Viral RNA Synthesis by SARS-CoV-2 RdRp
Jianyuan Zhao[SUP] 1 [/SUP], Yongxin Zhang[SUP] 1 [/SUP], Minghua Wang[SUP] 1 [/SUP], Qian Liu[SUP] 1 [/SUP], Xiaobo Lei[SUP] 2 [/SUP], Meng Wu[SUP] 3 [/SUP], SaiSai Guo[SUP] 1 [/SUP], Dongrong Yi[SUP] 1 [/SUP], Quanjie Li[SUP] 1 [/SUP], Ling Ma[SUP] 1 [/SUP], Zhenlong Liu[SUP] 4 [/SUP], Fei Guo[SUP] 2 [/SUP], Jianwei Wang[SUP] 2 [/SUP], Xiaoyu Li[SUP] 1 [/SUP], Yucheng Wang[SUP] 1 [/SUP], Shan Cen[SUP] 1 [/SUP]
Affiliations
- PMID: 34038639
- DOI: 10.1021/acsinfecdis.1c00083
Abstract
Coronavirus disease 2019 (COVID-19) is a fatal respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The identification of potential drugs is urgently needed to control the pandemic. RNA dependent RNA polymerase (RdRp) is a conserved protein within RNA viruses and plays a crucial role in the viral life cycle, thus making it an attractive target for development of antiviral drugs. In this study, 101 quinoline and quinazoline derivatives were screened against SARS-CoV-2 RdRp using a cell-based assay. Three compounds I-13e, I-13h, and I-13i exhibit remarkable potency in inhibiting RNA synthesis driven by SARS-CoV-2 RdRp and relatively low cytotoxicity. Among these three compounds, I-13e showed the strongest inhibition upon RNA synthesis driven by SARS-CoV-2 RdRp, the resistance to viral exoribonuclease activity and the inhibitory effect on the replication of CoV, thus holding potential of being drug candidate for treatment of SARS-CoV-2.
Keywords: COVID-19; Quinoline and quinazoline derivatives; RdRp inhibitors; SARS-CoV-2